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Effect of iron deficiency on c-kit⁺ cardiac stem cells in vitro
Dongqiang Song1, Yuanmin Li, Jiatian Cao
1Department of Cardiology, Ninth People's Hospital, Shanghai Jiaotong University Medical School, Shanghai, PR China.
Insights
Iron deficiency impairs cardiac stem cell proliferation and differentiation, potentially worsening chronic heart failure. Restoring iron levels may help mitigate these effects and improve heart function.
Area of Science:
- Cardiovascular Biology
- Stem Cell Research
- Iron Metabolism
Background:
- Iron deficiency is a common comorbidity in chronic heart failure (CHF), potentially exacerbating the condition.
- Cardiac stem cells (CSCs) are crucial for cardiac repair, but the impact of iron deficiency on their function is poorly understood.
Purpose of the Study:
- To investigate the effects of iron deficiency on the proliferation, migration, apoptosis, and differentiation of c-kit⁺ cardiac stem cells (CSCs) in vitro.
- To determine if iron supplementation can reverse the effects of iron deficiency on CSCs.
Main Methods:
- Isolated c-kit⁺ CSCs from adult mice.
- Treated CSCs with iron chelators (deferoxamine, mimosine) or iron-replete chelator.
- Assessed proliferation, cell cycle, apoptosis, migration, and expression of cardiac-specific and cell cycle proteins.
Main Results:
- Iron deficiency significantly suppressed CSC proliferation and differentiation.
- Iron chelators altered cell cycle protein expression and phosphorylation.
- Iron supplementation reversed the suppressive effects of iron deficiency.
- Iron deficiency did not affect CSC migration or apoptosis.
Conclusions:
- Iron deficiency negatively impacts c-kit⁺ CSC proliferation and differentiation.
- These findings may partially explain the detrimental role of iron deficiency in CHF prognosis.
- Targeting iron metabolism in CSCs could be a therapeutic strategy for CHF.
Aim:
Iron deficiency is a common comorbidity in chronic heart failure (CHF) which may exacerbate CHF. The c-kit⁺ cardiac stem cells (CSCs) play a vital role in cardiac function repair. However, much is unknown regarding the role of iron deficiency in regulating c-kit⁺ CSCs function. In this study, we investigated whether iron deficiency regulates c-kit⁺ CSCs proliferation, migration, apoptosis, and differentiation in vitro.
Method:
All c-kit⁺ CSCs were isolated from adult C57BL/6 mice. The c-kit⁺ CSCs were cultured with deferoxamine (DFO, an iron chelator), mimosine (MIM, another iron chelator), or a complex of DFO and iron (Fe(III)), respectively. Cell migration was assayed using a 48-well chamber system. Proliferation, cell cycle, and apoptosis of c-kit⁺ CSCs were analyzed with BrdU labeling, population doubling time assay, CCK-8 assay, and flow cytometry. Caspase-3 protein level and activity were examined with Western blotting and spectrophotometric detection. The changes in the expression of cardiac-specific proteins (GATA-4,TNI, and β-MHC) and cell cycle-related proteins (cyclin D1, RB, and pRB) were detected with Western blotting.
Result:
DFO and MIM suppressed c-kit⁺ CSCs proliferation and differentiation. They also modulated cell cycle and cardiac-specific protein expression. Iron chelators down-regulated the expression and phosphorylation of cell cycle-related proteins. Iron reversed those suppressive effects of DFO. DFO and MIM didn't affect c-kit⁺ CSCs migration and apoptosis.
Conclusion:
Iron deficiency suppressed proliferation and differentiation of c-kit⁺ CSCs. This may partly explain how iron deficiency affects CHF prognosis.
